This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a second revision of a collaborative R01 four-year competing continuation proposal to create a large repository-based sample of cases with recurrent, early-onset major depressive disorder &#40;MDD-RE&#41;, and to use positional cloning to identify depression susceptibility genes in regions of significant linkage in our genome scan. The completed four-year project collected 680 families containing 927 affected sibling pairs &#40;ASPs&#41;&#40;MDD-RE diagnostic model&#41;and additional affected relatives &#40;GenRED I&#41;. Blinded clinical data and blood specimens for cell culture were deposited in the NIMH repository and are being made public. Linkage fine-mapping has demonstrated genome-wide significant linkage on chromosome 15q;in the 10 cM genome scan, suggestive sex-specific linkage was observed in three regions &#40;6p-q, 8p, 17p&#41;, with the result on chromosome 17p approaching genome-wide significance. Six collaborating sites now propose to: &#40;1&#41;Collect &#40;during Years 1-3&#41;an additional 1,350 European-ancestry &#40;EUR&#41;MDD-RE probands &#40;GenRED II&#41;meeting identical criteria &#40;including evidence of having an affected sibling&#41;to create a total repository sample of 2,000 EUR MDD-RE cases, plus cell lines/DMA from available parents, unaffected sibs and male-male ASPs. &#40;2&#41;Initiate a repository-based collection of African-American &#40;AA&#41;MDD-RE probands meeting the same clinical criteria.